Mapping dopaminergic projections in the human brain with resting-state fMRI
Oldehinkel,Marianne Llera,Alberto Faber,Myrthe Huertas,Ismael Buitelaar,Jan K. Bloem,Bastiaan R. Marquand,Andre F. Helmich,Rick C. Haak,Koen Beckmann,Christian F.
Oldehinkel,Marianne
Llera,Alberto
Faber,Myrthe
Huertas,Ismael
Buitelaar,Jan K.
Bloem,Bastiaan R.
Marquand,Andre F.
Helmich,Rick C.
Haak,Koen
Beckmann,Christian F.
Abstract
The striatum receives dense dopaminergic projections, making it a key region of the dopaminergic system. Its dysfunction has been implicated in various conditions including Parkinson’s disease (PD) and substance use disorder. However, the investigation of dopamine-specific functioning in humans is problematic as current MRI approaches are unable to differentiate between dopaminergic and other projections. Here, we demonstrate that ‘connectopic mapping’-a novel approach for characterizing fine-grained, overlapping modes of functional connectivity-can be used to map dopaminergic projections in striatum. We applied connectopic mapping to resting-state functional MRI data of the Human Connectome Project (population cohort; N=839) and selected the second-order striatal connectivity mode for further analyses. We first validated its specificity to dopaminergic projections by demonstrating a high spatial correlation (r=0.884) with dopamine transporter availability-a marker of dopaminergic projections-derived from DaT SPECT scans of 209 healthy controls. Next, we obtained the subject-specific second-order modes from 20 controls and 39 PD patients scanned under placebo and under dopamine replacement therapy (L-ÐOPA), and show that our proposed dopaminergic marker tracks PD diagnosis, symptom severity, and sensitivity to L-ÐOPA. Finally, across 30 daily alcohol users and 38 daily smokers, we establish strong associations with self-reported alcohol and nicotine use. Our findings provide evidence that the second-order mode of functional connectivity in striatum maps onto dopaminergic projections, tracks inter-individual differences in PD symptom severity and L-ÐOPA sensitivity, and exhibits strong associations with levels of nicotine and alcohol use, thereby offering a new biomarker for dopamine- related (dys)function in the human brain.
Description
Funding Information: We made use of HCP data that were provided by the Human Connectome Project, WU-Minn Consortium (principal investigators: David Van Essen and Kamil Ugurbil; 1U54MH091657) funded by the 16 NIH Institutes and Centres that support the NIH Blueprint for Neuroscience Research; and by the McDonnell Centre for Systems Neuroscience at Washington University. We also used data from the Parkinson’s Progression Markers Initiative (PPMI) database (https://www.ppmi-info.org/data). PPMI – a public–private partnership – is funded by the Michael J Fox Foundation for Parkinson’s Research funding partners Abbvie, Avid Radiopharmaceuticals, Biogen Idec, BioLegend, Bristol-Myers Squibb, Eli Lilly & Co., F Hoffman-La Roche, Ltd., GE Healthcare, Genentech, GlaxoSmithKline, Lundbeck, Merck, MesoScale Discovery, Piramal, Pfizer, Sanofi Genzyme, Servier, Takeda, Teva, and UCB. We further used PET scans available in the JuSpace toolbox: https://github.com/juryxy/JuSpace (Dukart et al., 2021). Publisher Copyright: © Oldehinkel et al.
Date
2022-02-03
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Keywords
Adult, Aged, Aged, 80 and over, Biomarkers/analysis, Brain/diagnostic imaging, Cohort Studies, Corpus Striatum/diagnostic imaging, Dopamine Plasma Membrane Transport Proteins/physiology, Dopamine/metabolism, Female, Humans, Levodopa/therapeutic use, Magnetic Resonance Imaging/methods, Male, Middle Aged, Neural Pathways/physiopathology, Parkinson Disease/diagnostic imaging, SDG 3 - Good Health and Well-being
Citation
Oldehinkel, M, Llera, A, Faber, M, Huertas, I, Buitelaar, J K, Bloem, B R, Marquand, A F, Helmich, R C, Haak, K & Beckmann, C F 2022, 'Mapping dopaminergic projections in the human brain with resting-state fMRI', Elife, vol. 11, e71846, pp. 1-37. https://doi.org/10.7554/ELIFE.71846